Pharmacodynamics of [D-Ser (t-Bu), Des-Gly]GnRH ethylamide (Buserelin®) in 6 normal volunteers.

1987 ◽  
Vol 115 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Y. Reznik ◽  
B. P. Winiger ◽  
M. L. Aubert ◽  
P. C. Sizonenko

Abstract. The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin®, HOE 766) was studied in plasma and urine after intranasal (300 μg) or sc (10 μg/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (± sem) was 0.46 ± 0.08, 0.50 ± 0.10, 0.28 ± 0.04, 0.24 ± 0.04, 0.13 ± 0.03, and 0.08 ± 0.02 μg/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 ± 1.96 μg/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 ± 3.0, 25.9 ± 0.8, 21.2 ± 0.9, 17.1 ± 0.7, 12.8 ± 1.1, 8.9 ± 0.4, and 5.9 ± 0.8 μg/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 ± 61 μg/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17β-E2and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty.

1970 ◽  
Vol 63 (4) ◽  
pp. 705-716 ◽  
Author(s):  
U. Larsson-Cohn ◽  
E. D. B. Johansson ◽  
L. Wide ◽  
C. Gemzell

ABSTRACT Daily determinations of the plasma level of progesterone and the urinary excretion of luteinizing hormone (LH) and total oestrogens were performed in 6 subjects during one control cycle, immediately followed by three cycles of daily treatment with 0.5 mg of chlormadinone acetate continuously. The control cycles were ovulatory according to the parameters investigated. Two of the women showed a normal LH excretion pattern in all treatment cycles. The four other subjects also had periodical variations in the LH excretion but no distinct midcycle peaks occurred. The mean oestrogen excretion was increased in all three treatment cycles but the difference was satistically significant only in the last two cycles. Compared with the treatment cycles, the sum of progesterone values was significantly decreased in the first two cycles. Chlormadinone acetate in this dose had no thermogenic effect. Three of the subjects showed bleeding irregularities which had no clear connection with the hormone variations measured in the study. It is suggested that the low levels of progesterone might be due to a defective corpus luteum function.


1971 ◽  
Vol 68 (3) ◽  
pp. 502-512 ◽  
Author(s):  
Elof D. B. Johansson ◽  
Leif Wide ◽  
Carl Gemzell

ABSTRACT The plasma levels of luteinizing hormone (LH) and progesterone and the urinary excretion of LH and oestrogens were measured during the normal menstrual cycle of 22 young and healthy women. A total of 42 cycles were investigated. The urinary excretion of total oestrogens increased during several days before the rise of LH in the urine. The day of maximum excretion of LH and total oestrogens coincided during the midcycle period. The mid-cyclic rise in LH was found to occur on the same day in the plasma and urine and the days of maximum values coincided in 11 out of 16 cycles. In 5 cycles the maximum level was reached one day later in the urine. The plasma levels of progesterone started to increase during the LH and oestrogen peaks. The days for maximum levels of progesterone coincided with the second peak of urinary oestrogens. The levels of progesterone in the plasma reached values above 10 ng per ml in all normal cycles. The plasma levels of progesterone were below 1 ng per ml plasma when menstrual bleeding started. The length of the luteal phase was 14.4 ± 1.1 (s) days. The sum of daily urinary excretion of total oestrogens and the sum of the daily plasma progesterone levels varied within 15 per cent of the mean in five out of six women studied during more than two cycles. The variation in values for the sums of daily oestrogen excretion and plasma progesterone levels was considerably larger between menstrual cycles of different women than between menstrual cycles of the same woman.


1972 ◽  
Vol 71 (3) ◽  
pp. 551-556 ◽  
Author(s):  
Ulf Larsson-Cohn ◽  
Elof D. B. Johansson ◽  
Leif Wide ◽  
Carl Gemzell

ABSTRACT Daily determinations of the plasma level of progesterone and the urinary excretion of LH and oestrogens were performed in four women during one control cycle followed by three months of daily treatment with 0.1 mg of norethindrone. According to the plasma progesterone pattern, all four women seemed to ovulate during their control cycle. Two women became pregnant during their second cycle of treatment. During treatment all four women showed an atypical LH pattern without any distinct midcycle peak. The mean LH excretion during treatment was not significantly different from the mean level of follicular phase of normal cycles. The oestrogens and progesterone levels were within normal ranges. It is concluded that during treatment with 0.1 mg of norethindrone daily an apparently normal pregnancy may occur in spite of a different LH excretion pattern.


1975 ◽  
Vol 64 (3) ◽  
pp. 521-528 ◽  
Author(s):  
B. T. DONOVAN ◽  
M. B. TER HAAR ◽  
A. N. LOCKHART ◽  
M. J. PEDDIE

SUMMARY The concentration of FSH in the plasma of guinea-pigs from day 50 of gestation to day 45 of postnatal life was assayed by a radioimmunological procedure utilizing a cross-reaction with the NIAMDD S6 antiserum to rat FSH. At 68 days of gestation the mean plasma FSH concentration of female foetuses was greater than that of the males, although the concentrations in the two sexes were similar on day 50 of gestation. Maternal levels remained consistently low throughout gestation. Postnatally there were no marked changes in plasma FSH levels through to maturity, although a transient rise in the male occurred over the first 3 days after birth. Gonadectomy on days 0, 5, 10, 15, 25 or 35 of postnatal life, or when adult, resulted in a significant increase in plasma levels of FSH within 10 days. The rise in plasma FSH concentration was greater in males than in females at all ages, although a larger increase was observed in females spayed at 5 or 10 days of age than at other times.


1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.


1966 ◽  
Vol 16 (01/02) ◽  
pp. 038-050 ◽  
Author(s):  
Ulla Hedner ◽  
Inga Marie Nilsson ◽  
B Robertson

SummaryThe plasminogen content was determined by a casein method in plasma and serum from 20 normal volunteers. The mean plasminogen content was found to be 10.1 ACU (the arbitrary caseinolytic unit defined in such a way that using a 3% casein solution and a digestion time of 20 min. at 37°C, 10 ACU gave an extinction of 0.300). No difference between serum and plasma regarding the plasminogen content was found.Plasminogen was determined in drained and drained plus washed clots prepared from 2 ml plasma. The highest values found in the drained clots were 0.9 ACU/clot and 0.2 ACU/clot in the drained plus washed clots.Plasminogen was also determined in drained and drained plus washed clots prepared from plasma with added purified plasminogen. The plasminogen was recovered in the washing fluid. According to these tests, then, purified added plasminogen is washed out of the clots.The plasminogen content of 20 thrombi obtained post mortem was also determined. The mean value was found to be 0.7 ACU/cm thrombus. Judging from our results, the “intrinsic clot lysis theory” is not the main mechanism of clot dissolution.


1966 ◽  
Vol 53 (2) ◽  
pp. 177-188 ◽  
Author(s):  
P. Lund-Johansen ◽  
T. Thorsen ◽  
K. F. Støa

ABSTRACT A comparison has been made between (A), a relatively simple method for the measurement of aldosterone secretion rate, based on paper chromatography and direct densitometry of the aldosterone spot and (B) a more elaborate isotope derivative method. The mean secretion rate in 9 normal subjects was 112 ± 26 μg per 24 hours (method A) and 135 ± 35 μg per 24 hours (method B). The »secretion rate« in one adrenalectomized subject after the intravenous injection of 250 μg of aldosterone was 230 μg per 24 hours (method A) and 294 μg per 24 hours (method B). There was no significant difference in the mean values, and correlation between the two methods was good (r = 0.80). It is concluded that the densitometric method is suitable for clinical purposes as well as research, being more rapid and less expensive than the isotope derivative method. Method A also measures the urinary excretion of the aldosterone 3-oxo-conjugate, which is of interest in many pathological conditions. The densitometric method is obviously the less sensitive and a prerequisite for its use is an aldosterone secretion of 20—30 μg per 24 hours. Lower values are, however, rare in adults.


1974 ◽  
Vol 75 (4) ◽  
pp. 647-652 ◽  
Author(s):  
G. Rannevik ◽  
J. Thorell

ABSTRACT Eight amenorrhoeic women were given 100 μg synthetic LRH (Hoechst) iv and im, respectively, at an interval of 2 weeks. Four of the women received the iv injection first and four the im injection. The urinary excretion of oestrogens and pregnanediol was low and unaltered throughout the test weeks. The effects of LRH were compared by serial measurements of the plasma LH and FSH during 8 h. The initial response of LH for up to 25 min and that of FSH for up to 60 min were equal whether LRH was given iv or im. The difference appeared later. Four hours after the injection the mean increase of LH to iv injection was 0.5 ng/ml (N. S.), while that to im injection was 1.9 ng/ml (P < 0.01). The corresponding values for FSH were 1.3 (P < 0.05) and 3.2 (P < 0.001). The effect of LRH administration im was thus found to be larger and more prolonged.


1970 ◽  
Vol 64 (2) ◽  
pp. 265-272 ◽  
Author(s):  
A. A. van der Gugten ◽  
M. Sala ◽  
H. G. Kwa

ABSTRACT Eight female and eight male rats were castrated at the age of 8 to 10 weeks. Four spayed and four orchidectomized rats received one oestrone/cholesterol pellet (200 μg oestrone) on the day of operation (day 0), a second pellet on day 11 and a third on day 23. The remaining animals received four oestrone/cholesterol pellets at these times. The fluctuations in the prolactin levels in the circulation induced by the oestrogen challenges in these animals were followed during 31 days by radioimmunoassays performed on days 3, 7, 9, 14, 15, 17, 23, 24, 25, 28 and 31. The results suggested that the homoeostatic mechanism regulating plasma levels of prolactin was capable of withstanding the three time-spaced oestrogen challenges only in the spayed animals receiving the lower doses of oestrogen, since it allowed the mean values of the prolactin levels to remain fairly constant during the first 4 weeks. The levels in this group rose to much higher levels only on day 31. The higher doses of oestrone in the spayed rats and both dose levels of oestrone in the orchidectomized animals apparently resulted in a primary break-down of the homoeostatic mechanism, since the prolactin levels in the animals of these groups rose to much higher levels either on day 7 or on day 9. This was followed by a period during which the prolactin levels appeared to be more or less under control, until a second and probably definitive failure of the homoeostatic mechanism allowed the mean levels to rise sharply again.


2019 ◽  
Vol 15 (02) ◽  
pp. 14-17
Author(s):  
K K Hadiya ◽  
A J Dhami ◽  
D V Chaudhari ◽  
P M Lunagariya

This study was initiated on 24 prepubertal Holstein x Kankrej crossbred heifers of nearly identical age (7-9 months) and body weight (130-140 kg) at University farm to evaluate the effect of high plane of nutrition on blood biochemical and minerals profile and the age at puberty. Twelve heifers were managed under routine farm feeding (control) and the rest 12 under ideal optimum feeding regime (treatment) that included extra 1 kg concentrate, 30 g min mix and ad-lib dry fodder. The body weight and ovarian ultrasonography together with blood sampling was carried out at monthly interval from 10 to 18 months of age to study the ovarian dynamics and blood biochemical changes. High plane of nutrition to growing heifers was beneficial in reducing the age of onset of puberty (by 2-3 months) compared to routine farm fed group. The mean plasma total protein and cholesterol concentrations showed a rising trend with significant variations from 10 to 16 months of age, where it got mostly stabilized indicating adult profile. The activity of enzymes GOT and GPT also rose gradually and significantly from 10 months till 14-15 months of age, and thereafter it remained more or less static till 18 months of age. The levels of both these enzymes were higher, with lower protein and cholesterol, in control than the treatment group from 15-16 months of age onwards. The mean plasma levels of both calcium and phosphorus increased gradually and significantly with advancing age till 16-17 months of age, with little higher values in supplemented than a control group. The plasma levels of zinc, iron, copper, and cobalt also showed rising trend with significant differences between 10th and 12th-14th months of age, and from 15th to 18th months of age the levels were statistically the same in all the groups with slightly higher values in the treatment group.


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